The cellular response of rats to Listeria monocytogenes (LM) and other intracellular bacterial parasites would be studied with a view to ascertaining the type(s) of T cells which mediate delayed-type hypersensitivity (DTH) and acquired cellular resistance to infection, the constraints imposed on mediator T cells by determinants coded within the major histocompatibility complex, and factors which regulate the T cell response to infection. The proposed studies would endeavor to substantiate and extend observations which suggest that cellular resistance to LM is mediated in rats by at least two populations of T cells. To this end, experiments would be undertaken in genetically defined SPF rats using relatively new methods for identifying T cells and T cell subsets in this species. Regulation of the T cell response to LM would be analyzed in adoptively immunized subjects. The hypothesis would be tested that suppressor T cells have an immunoregulatory function in infected rats; however, the possibility that other factors influence the T cell response to infection would also be investigated. Finally, we would pursue the recent observation that TDL from LM-immune rats can be stimulated in vitro to replicate and generate cells which are cytotoxic for Listeria-antigen-senstitized target cells. Here the focus of research would be on the identity of responder lymphocytes, the MHC constraints, if any, which limit their proliferation and cytotoxic activity, and the capacity of in vitro stimulated T cells to operate as suppressors or as mediators of DTH, cellular resistance in the intact animal.